All substances activate the same brain reward pathway via dopaminergic neurotransmission. 5 Individuals who demonstrate a chronic loss of control or compulsive use of substances along with a wide range of negative effects (mental, physical, and social well-being) meet the criteria for substance related disorders. 3 Standardized screening is important to determine the stage of substance use, consequences, and functional impairment. 5 Controlled Substance Act (CSA) The Comprehensive Drug Abuse Prevention and Control Act of 1970 , or the Controlled Substance Act (CSA), regulates pharmaceutical and illicit controlled substances in the United States 2010 Statement of Policy: Role of Authorized Agents in Communicating Controlled Substance Prescriptions to Pharmacies. 6 The CSA requires registration, outlines specific rules about dispensing pharmaceutical controlled substances, and determines the legality of these substances. The U.S. Drug Enforcement Agency (DEA) was formed in 1973 to enforce the CSA. For pharmaceutical controlled substances, the DEA is responsible for preventing the diversion and abuse of controlled drug substances. The agency also ensures that an adequate and uninterrupted supply of pharmaceutical controlled substances is available to meet legitimate medical, scientific, and research needs. Along with state and other federal agencies, the DEA regulates the registration of manufacturers, distributors, and dispensers of controlled pharmaceutical substances and the import and export of these substances. The DEA prosecutes anyone who violates this law. 7 The U.S. federal agencies involved in scheduling controlled substances include the Drug Enforcement Agency (DEA), Food and Drug Administration (FDA), and Department of Health and Human Services (HHS). Drugs and other substances that are considered controlled substances under the CSA are divided into five schedules. Substances are placed in their respective schedules based on whether they have a currently accepted medical use in treatment in the United States, their relative abuse potential, and the likelihood of causing dependence when abused. • Schedule I Controlled Substances.
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Schedule IV Controlled Substances. Substances in this schedule have a low potential for abuse relative to substances in Schedule III. Schedule V Controlled Substances. Substances in this schedule have a low potential for abuse relative to substances listed in Schedule IV and consist primarily of preparations containing limited quantities of certain narcotics. Neurobiology of Substance Use Disorders
Substance-Related Disorders Substance use disorders are a significant public health problem with a wide range of negative effects on individuals’ mental, physical, and social well-being. Mental health problems co-occurring with substance use disorders include depressive, anxiety, and psychotic disorders, as well as organic brain syndromes. 2 Substance use disorders share many of the same features but differ in pharmacology and associated behaviors that account for the unique effects of each substance. 3 The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision , often called the DSM-V-TR or DSM-5-TR, is the latest version of the American Psychiatric Association’s publication defining various conditions. 4 The DSM-5-TR recognizes substance-related disorders resulting from the use of 10 separate classes of substance including the following: • Alcohol • Caffeine • Cannabis • Hallucinogens • Inhalants • Opioids • Sedatives • Hypnotics or anxiolytics • Stimulants (including amphetamine-type substances, cocaine, and other stimulants) • Tobacco The criteria used to diagnose and define substance use disorders spans a wide variety of problems arising from substance use, and they include the following: 1. Taking the substance in larger amounts or for longer than meant to 2. Wanting to cut down or stop using the substance but not managing to 3. Spending a lot of time getting, using, or recovering from use of the substance 4. Cravings and urges to use the substance 5. Not managing responsibilities at work, home, or school because of substance use 6. Continued use, even when it causes problems in relationships 7. Giving up important social, occupational, or recreational activities because of substance use 8. Using substances repeatedly, even after negative outcomes 9. Continued use, even when physical or psychological problem have been caused or complicated by the substance 10. Seeking more of the substance to get the effect you want (tolerance) 11. Development of withdrawal symptoms that are relieved by taking more of the substance The hallmark of substance use disorders includes cognitive, behavioral, and physiological symptoms of intoxication, withdrawal, and dependence. 4 Diagnosis is based on pathological patterns of substance use.
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Substance use disorders (SUDs) are complicated physiologic and psychological disorders with multiple intersecting factors, such as drug use behaviors and poor judgment influenced by the pharmacodynamics and pharmacokinetic actions of the drug. The central element of drug dependence is the drug-using behavior. Drug use initiates a cascade of rewarding or aversive physical, psychological, and social consequences that determine the likelihood of subsequent use. 8 The development and persistence of SUDs are largely based on key components within the basal ganglia, amygdala (extended), and prefrontal cortex. The basal ganglia and its sub-networks are responsible for reward, pleasure, and formation of habitual substance use. 9 The amygdala is responsible for the uneasy feelings, anxiety, and irritability associated with withdrawal. The prefrontal cortex is involved in executive function and exerts control over the individual’s cognitive inability to reject substance use based on neurocircuitry, namely impulsivity and compulsivity. 10 These endophenotypes are found transdiagnostically across many psychopathologies. Impulsivity, when characterized as the failure to resist a drive or impulse potentially harmful to the self or others, is a core feature of several psychiatric disorders, including substance use disorder. 11 Impulsivity causes the individual to act without forethought, unable to reflect on previous behavior and seek immediate reward by choosing risky behavior. Compulsivity is characterized by inappropriate actions which persist regardless of the situation. Over time, impulsive substance use becomes compulsive addiction as this dysregulation becomes a dependent conditioned response. The impulses in the ventral loop of reward and motivation migrate dorsally because of neuroplasticity and engage in a habit system, creating the conditioned response of addiction. 12 Impulsive drug use produces a high , which if experienced too often causes the migration to compulsive use (addiction) to reduce the unpleasant effects of withdrawal. The mesolimbic pathway is hypothesized to be the final common pathway of reward and reinforcement in the brain, where all addictive drugs increase dopamine, especially with habitual use. 13 Arising in the ventral tegmental area (VTA), it projects into the nucleus accumbens (NA) and prefrontal cortex (PFC).
Substances in this schedule have no currently accepted medical use in the United States, a lack of accepted safety for use under medical supervision, and a high potential for abuse. Schedule II/IIN Controlled Substances (2/2N). Substances in this schedule have a high potential for abuse, which may lead to severe psychological or physical dependence. Schedule III/IIIN Controlled Substances (3/3N). Substances in this schedule have a potential for abuse less than substances in Schedules I or II and abuse may lead to moderate or low physical dependence or high psychological dependence.
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